The objective of this study is to investigate the possibility that elevated rates of cancer of operating room personnel and increased mortality and morbidity among their offspring may relate to modifications of chromosomal proteins by reactive anesthetic metabolites. Histones and other chromosomal proteins are involved in the control of genetic expression. Extensive modifications of nuclear proteins by methylation, acetylation and phosphorylation result from various hormonal stimuli or accompany stages of cellular differentiation and development. Metabolites of organohalogen anesthetics may be highly reactive and capable of alkylation of chromosomal proteins. We propose that non-specific modification of chromosomal protein by anesthetic metabolites will deleteriously effect genetic expression with potential teratogenic or carcinogenic consequences. Anesthetics will initially be incubated with homogenates of regenerating liver or administered to partially hepatectomized animals prior to isolation chromatin. Purified chromatin, histones and non-histone chromosomal proteins will be assayed for binding of anesthetic metabolites. Controls will be used as a reference to detect any changes in electrophoretic chromosomal protein banding patterns due to exposure to anesthetics. This work could provide a new screening test for predicting the teratogenic or carcinogenic potential of anesthetics or related organohalogen drugs based upon alkylation of chromosomes by reactive metabolic intermediates of these compounds.